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Guzel F Zakyrjanova^1,2, Valeriya A Matigorova¹, Eva A Kuznetsova¹

¹Kazan Institute of Biochemistry and Biophysics, Federal Research Center "Kazan Scientific Center of RAS", 2/31 Lobachevsky Street, Box 30, Kazan, 420111, Russia.

Archives of toxicology

|April 15, 2025

概括

阿托瓦斯塔丁通过增加氧化应激和炎症,对隔膜肌肉产生负面影响,同时降低线粒体功能和蛋白质合成. 这些与他类药物相关的肌肉症状 (SAMS) 可能源于细胞过程中出现的干扰.

科学领域:

生物化学生物化学
分子生物学分子生物学
生理学生理学生理学

背景情况:

类药物被广泛用于预防心血管疾病.
类他类药物相关的肌肉症状 (SAMS) 是常见的,但其机制尚不清楚.
类他类药物抑制了美酸盐路径,影响胆固醇和其他重要的分子合成.

研究的目的:

为了研究与他类药物相关的肌肉症状 (SAMS) 背后的分子机制.
评估阿托瓦斯塔丁对小鼠腹膜肌的影响.
为了识别受到他类药物治疗影响的细胞过程.

主要方法:

鼠标腹膜的整个转录组序列.
光,生化和组织学分析.
艾托瓦斯塔丁在临床相关剂量内口服给小鼠一个月.

主要成果:

阿托尔瓦斯塔丁降低了氧化酸化和合成代谢过程的基因调节.
与炎症和肌肉缩相关的基因被上调.
观察到线粒体极化减少,蛋白质合成减少,脂质过氧化增加和反应性氧物种的产生.
阿托瓦斯塔丁治疗破坏了脂质,引起了脂症,髓脱凝和肌肉纤维异质.

结论:

阿托瓦斯塔丁通过氧化应激,线粒体活性降低和蛋白质合成受损,对隔膜肌肉产生负面影响.
血的稳定性受到损害,导致SAMS.
补偿反应包括增加的超氧化物脱酶活性和胆固醇吸收.

关键词:

胆固醇胆固醇胆固醇线粒体中的线粒体.氧化应激是一种氧化应激.骨肌肉缩骨肌肉缩史塔丁类药物是一种

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